In the heart catecholamines produce an increase in contractility and glycogenolysis. Adenosine 3',5'-monophosphate (cyclic AMP) appears to be important in mediating the mechanical and metabolic effects. Adenosine, another naturally occurring compound that is a potent coronary vasodilatory and continually released from the myocardium, appears to play an important role in the regulation of coronary blood flow when demands for oxygen by the heart increase such as in the case with catecholamine stimulation. It is the purpose of this project to study the modulation of catecholamine induced increases in cardiac contractility and glycogenolysis caused by adenosine. The working hypothesis is that in addition to serving as an important vasoactive metabolite controlling coronary flow, adenosine serves as a negative-feedback regulator controlling the formation of cyclic AMP elicited by catecholamines. The hypothesis will be investigated by studying the effects of adenosine on cyclic AMP formation in response to catecholamine stimulation in the isolated working heart preparation of the rat. The effects of the nucleoside on contractility and the enzymes involved in glycogenolysis will be determined. To investigate the mechanism of action of adenosine the effects of the nucleoside on adenylate cyclase and phosphodiesterase, the enzymes responsible for cyclic AMP synthesis and degradation, respectively will be studied. The role of calcium in the action of adenosine will also be investigated. The production of endogenous adenosine and its importance in feedback regulation of catecholamine induced cyclic AMP formation will be determined. Ultimately, the effects of adenosine on cyclic AMP formation in the anoxic and hypertrophied heart will be studied.